Arrays of integrated analytical devices and methods for production

Abstract

Arrays of integrated analytical devices and their methods for production are provided. The arrays are useful in the analysis of highly multiplexed optical reactions in large numbers at high densities, including biochemical reactions, such as nucleic acid sequencing reactions. The integrated devices allow the highly sensitive discrimination of optical signals using features such as spectra, amplitude, and time resolution, or combinations thereof. The arrays and methods of the invention make use of silicon chip fabrication and manufacturing techniques developed for the electronics industry and highly suited for miniaturization and high throughput.

What is claimed is: 
     
       1. An array of integrated analytical devices comprising:
 a substrate layer, wherein the substrate layer is a detector layer; 
 a waveguide module layer disposed above the substrate layer, wherein the waveguide module layer comprises a lower waveguide cladding material, a waveguide core material, and an upper waveguide cladding material; and 
 a zero-mode waveguide module layer disposed on the waveguide module layer, wherein the zero-mode waveguide module layer comprises a plurality of nanometer-scale apertures penetrating to the waveguide module layer; 
 wherein at least one analytical device comprises a single detector element in the detector layer, and wherein the single detector element is optically coupled to a single nanometer-scale aperture through the waveguide module layer. 
 
     
     
       2. The array of  claim 1 , wherein the detector layer is a CMOS wafer. 
     
     
       3. The array of  claim 1 , wherein the single detector element comprises one pixel. 
     
     
       4. The array of  claim 1 , wherein the array does not comprise a color separation layer. 
     
     
       5. The array of  claim 1 , wherein the upper waveguide cladding material is SiO 2 . 
     
     
       6. The array of  claim 1 , wherein the waveguide core material is Si 3 N 4 . 
     
     
       7. The array of  claim 1 , wherein at least one of the plurality of nanometer-scale apertures comprises a fluid sample comprising a fluorescent species. 
     
     
       8. The array of  claim 7 , wherein the fluorescent species is a fluorescently labeled nucleotide analog. 
     
     
       9. The array of  claim 7 , wherein the fluid sample comprises a plurality of fluorescent species having distinct signal intensities. 
     
     
       10. The array of  claim 1 , wherein the plurality of nanometer-scale apertures comprise at least 100 nanometer-scale apertures. 
     
     
       11. The array of  claim 1 , wherein the plurality of nanometer-scale apertures have a density of at least 1000 apertures per cm 2 . 
     
     
       12. The array of  claim 1 , further comprising a filter module layer disposed between the detector layer and the waveguide module layer. 
     
     
       13. The array of  claim 12 , wherein the filter module layer comprises a dielectric filter. 
     
     
       14. The array of  claim 12 , wherein the filter module layer comprises an absorptive filter. 
     
     
       15. The array of  claim 1 , wherein the plurality of nanometer-scale apertures is formed by etching, and the etching is stopped using an endpoint signal. 
     
     
       16. The array of  claim 1 , wherein at least one nanometer-scale aperture fully penetrates the upper waveguide cladding material. 
     
     
       17. The array of  claim 16  wherein the at least one nanometer-scale aperture is partially backfilled. 
     
     
       18. The array of  claim 17 , wherein the at least one nanometer-scale aperture is partially backfilled using atomic layer deposition or low pressure chemical vapor deposition. 
     
     
       19. The array of  claim 1 , further comprising an etch hardmask. 
     
     
       20. An analytical system for the simultaneous measurement of multiple reactions comprising:
 the array of integrated analytical devices of  claim 1 ; and 
 an excitation light source. 
 
     
     
       21. The analytical system of  claim 20 , wherein the excitation light source is coupled to the array of integrated analytical devices through an optical coupler integrated in the array. 
     
     
       22. The analytical system of  claim 20 , wherein the system comprises a single excitation source.